Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance
It is well known that dendritic cells (DCs) play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs), a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment...
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| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/5021537 |
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| author | Yan Zhou Xiao Leng Shasha Luo Zhiwei Su Xingyan Luo Huijie Guo Chunfen Mo Qiang Zou Yang Liu Yantang Wang |
| author_facet | Yan Zhou Xiao Leng Shasha Luo Zhiwei Su Xingyan Luo Huijie Guo Chunfen Mo Qiang Zou Yang Liu Yantang Wang |
| author_sort | Yan Zhou |
| collection | DOAJ |
| description | It is well known that dendritic cells (DCs) play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs), a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG-) specific experimental autoimmune encephalomyelitis (EAE) model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS). Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT) disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs). Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS. |
| format | Article |
| id | doaj-art-041c1e2ebbe24910a2a4e9c8cb5326ae |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-041c1e2ebbe24910a2a4e9c8cb5326ae2025-08-20T02:03:05ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/50215375021537Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg BalanceYan Zhou0Xiao Leng1Shasha Luo2Zhiwei Su3Xingyan Luo4Huijie Guo5Chunfen Mo6Qiang Zou7Yang Liu8Yantang Wang9Department of Pediatrics and Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610083, ChinaDepartment of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610083, ChinaDepartment of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610083, ChinaDepartment of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610083, ChinaDepartment of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610083, ChinaDepartment of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610083, ChinaDepartment of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610083, ChinaDepartment of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610083, ChinaDepartment of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610083, ChinaIt is well known that dendritic cells (DCs) play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs), a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG-) specific experimental autoimmune encephalomyelitis (EAE) model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS). Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT) disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs). Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS.http://dx.doi.org/10.1155/2016/5021537 |
| spellingShingle | Yan Zhou Xiao Leng Shasha Luo Zhiwei Su Xingyan Luo Huijie Guo Chunfen Mo Qiang Zou Yang Liu Yantang Wang Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance Journal of Immunology Research |
| title | Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance |
| title_full | Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance |
| title_fullStr | Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance |
| title_full_unstemmed | Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance |
| title_short | Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance |
| title_sort | tolerogenic dendritic cells generated with tofacitinib ameliorate experimental autoimmune encephalomyelitis through modulation of th17 treg balance |
| url | http://dx.doi.org/10.1155/2016/5021537 |
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